Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, very few studies have been published on the role of acetaldehyde in the ... [more ▼]

Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, very few studies have been published on the role of acetaldehyde in the amnesic and ataxic effects of ethanol. The aim of the present studies was to compare the profiles of ethanol and acetaldehyde in several behavioral tests, measuring motor coordination, learning and memory in mice. Female Swiss mice were injected intraperitoneally with ethanol (0-3g/kg) and acetaldehyde (100-300mg/kg). The effects of these substances on a series of representative behaviors were investigated. The amnesic effects were tested with an object recognition task and a one-trial passive avoidance test. Additionally, the rectal temperatures were used to evaluate the hypothermic effects of the two substances. Finally, motor coordination was assessed using the accelerating rotarod test. The results showed that acetaldehyde, like ethanol, altered memory as shown by a reduced performance in the passive avoidance test and the object recognition task. In addition, acetaldehyde at doses between 100 and 300 mg/kg induced significant hypothermic effects, but that was of shorter duration than ethanol-induced hypothermia. Finally, significant ataxic effects of both acetaldehyde and ethanol were observed in the accelerating rotarod test. Overall, the results of the present study clearly show that acetaldehyde, like ethanol, has amnesic, hypothermic and ataxic properties in mice at least at relatively high concentrations. [less ▲]

BACKGROUND: Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, few studies have investigated the hypothermic effects of ... [more ▼]

BACKGROUND: Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, few studies have investigated the hypothermic effects of acetaldehyde or the contribution of acetaldehyde to ethanol-induced hypothermia. The aim of the present study is to better understand the hypothermic effects of acetaldehyde and the possible contribution of acetaldehyde in ethanol-induced hypothermia, especially under conditions leading to acetaldehyde accumulation. METHODS: Female Swiss mice were injected intraperitoneally with ethanol and acetaldehyde and their rectal temperatures were measured with a digital thermometer at various time points after the injections. Experiment 1 compared the hypothermic effects of various acetaldehyde doses (0 to 300 mg/kg) with a reference dose of ethanol (3 g/kg). Experiment 2 tested the effects of a pretreatment with the aldehyde dehydrogenase (ALDH) inhibitor cyanamide (25 mg/kg) on ethanol- and acetaldehyde-induced hypothermia. In experiments 3 and 4, mice received a combined pretreatment with cyanamide and the alcohol dehydrogenase (ADH) inhibitor 4-Methylpyrazole (10 mg/kg) before the injection of ethanol or acetaldehyde. RESULTS: Acetaldehyde at doses between 100 and 300 mg/kg induced significant hypothermic effects, but of shorter duration than ethanol-induced hypothermia. The inhibition of ALDH enzymes by cyanamide induced a strong potentiation of both ethanol- and acetaldehyde-induced hypothermia. The pretreatment with 4-MP prevented the potentiation of ethanol-induced hypothermia by cyanamide, but slightly increased the potentiation of acetaldehyde-induced hypothermia by cyanamide. CONCLUSIONS: The results of the present study clearly show that acetaldehyde has hypothermic properties in mice at least at relatively high concentrations. Furthermore, the accumulation of acetaldehyde following ALDH inhibition strongly enhanced the hypothermic effects of ethanol. These latter results confirm the hypothermic properties of acetaldehyde and show that acetate, the next step in ethanol metabolism, is not involved in these hypothermic effects. Finally, the experiment with 4-MP indicates that the potentiating effects of cyanamide are mediated by the peripheral accumulation of acetaldehyde, which then reaches the brain to induce a severe hypothermia. [less ▲]

Whereas human studies keep reporting evidence that acetaldehyde accumulation prevents alcohol drinking and alcoholism, animal studies support a rewarding rather than aversive role for acetaldehyde. In ... [more ▼]

Whereas human studies keep reporting evidence that acetaldehyde accumulation prevents alcohol drinking and alcoholism, animal studies support a rewarding rather than aversive role for acetaldehyde. In recent years, the reinforcing properties of acetaldehyde were demonstrated in various rodent strains and using different experimental methods. These results led to the hypothesis that acetaldehyde might be involved in the addictive properties of alcohol. In addition to its possible role in the reinforcing properties of alcohol, there is also evidence that acetaldehyde is involved in many other behavioral effects of ethanol. Using various behavioral procedures with both mice and rats, we have studied the behavioral effects of direct acetaldehyde injections. Additionally, in independent experiments we have compared the effects of ethanol in mice with or without a pre-treatment with the aldehyde dehydrogenase inhibitor cyanamide, which produces acetaldehyde accumulation. The results of these studies show that acetaldehyde produces a wide spectrum of behavioral effects, including reinforcement, aversion, sedation, ataxia and amnesia. These effects were mainly dependent upon acetaldehyde doses, with some of them showing an inverted U shape dose-response curve. These results also suggest that acetaldehyde might mediate or contribute to many of the behavioral effects of ethanol and especially to alcohol abuse and alcoholism. [less ▲]